The present invention relates to certain new compositions and methods employing the known soil fungicide and plant growth regulator, 3-hydroxy-5-methylisoxazole, including, inter alia, a specific hydrate of the calcium salt of this compound.
3-Hydroxy-5-methylisoxazole, which is also known by the common name "hymexazol" and is sold by Sankyo Co. Ltd. under the trade name "Tachigaren", is disclosed, inter alia., in British Patent Specification No. 1 113 618. Subsequent British Patent Specifications No. 1 199 737 and 1 256 835 disclose other methods of preparing it and disclose its alkali metal salts. Japanese Patent Applications No. Sho 45-38953, Sho 45-72625, Sho 39-73350, Sho 45-29263 and Sho 45-108798 disclose various specific uses for this compound for the treatment or prevention of various plant diseases or as a plant growth regulator; these applications also disclose the calcium salt of 3-hydroxy-5-methylisoxazole as being especially useful, although no disclosure is made of any hydrate of the compounds. A complete review of the uses and activities of 3-hydroxy-5-methylisoxazole appears in Ann. Sankyo Res. Lab., 25, 1-51 (1973).
Soil-borne diseases affecting various kinds of crops and caused by soil-inhabiting pathogens have resulted in major problems for a long time in crop culture and agricultural administration, because they cause considerable damage and because they are difficult to control adequately. These problems have been made worse by the tendency, in recent years, to adopt schemes of intensive or mono-culture which result in a single type of crops being cultivated for many years continuously on the same soil, either in greenhouses or in open fields. As a consequence, occurrences of soil-borne diseases have greatly increased, and these have resulted in much damage and financial losses, since they can lead to a reduced or non-existent harvest. Typical soil inhabiting pathogens causing such soil-borne diseases include microorganisms belonging to the genera Fusarium, Pythium, Aphanomyces and Rhizoctonia.
3-Hydroxy-5-methylisoxazole is at present widely used to prevent a wide range of soil-borne diseases caused by such soil inhabiting pathogens because it is both effective and highly safe. For example, it is used, inter alia, for the prevention of seedling damping-off of rice and other crops caused by Pythium and Fusarium spp., Fusarium wilts of various crops caused by Fusarium sp. and sugar beat damping-off caused by Aphanomyces sp. 3-Hydroxy-5-methylisoxazole can prevent these soil-borne diseases not only by direct application to the soil treatment but also by treatment of seeds of potentially affected plants. For example, seed treatment with 3-hydroxy-5-methylisoxazole will very effectively control seedling damping off of sugar been caused by Aphanomyces and Pythium sp. Accordingly, a seed dressing of 3-hydroxy-5-methylisoxazole is widely used in Japan and in many European countries. In addition 3-hydroxy-5-methylisoxazole is known to have some physiological effects on various crop plants. For example, it will promote the growth of roots and will enhance the physiological activities of roots. Accordingly, it is very common in Japan to treat rice seeds with 3-hydroxy-5 -methylisoxazole prior to sowing them in flooded paddy fields; and it is known that this treatment is effective to stabilize the establishment of rice seedlings.
Furthermore, when 3-hydroxy-5-methylisoxazole and/or salts thereof are used in hydroponics, they show an algicidal effect against, for example, pond scum.
The calcium salt of 3-hydroxy-5-methylisoxazole is known, as mentioned in Japanese Patent Application Kokai No. Sho 48-38148, to have similar activities to 3-hydroxy-5-methylisoxazole itself against plant diseases affecting various kinds of crops. In addition, since the calcium salt of 3-hydroxy-5-methylisoxazole has a lower volatility than 3-hydroxy-5-methylisoxazole, the salt has practical advantages when used for seed treatment.
In soil, however, 3-hydroxy-5-methylisoxazole is rapidly decomposed by soil microorganisms. This is a factor which limits its residual effectiveness, as reported in Ann. Sankyo Res. Lab. 25, 42-45.
If the dose of 3-hydroxy-5-methylisoxazole is greatly increased in order to prolong the residual effectiveness, phytotoxicity, such as growth inhibition or delayed germination, may occur on the treated plant, especially with seed treatment. The calcium salt of 3-hydroxy-5-methylisoxazole is, in this respect also, better than 3-hydroxy-5-methylisoxazole, because the phytotoxicity caused by the calcium salt with seed treatment is lower than that caused by 3-hydroxy-5-methylisoxazole. However, if used in a large amount, even the calcium salt sometimes causes phytotoxicity. It is, therefore, difficult to prolong the residual effectiveness by much increasing the amount of 3-hydroxy-5-methylisoxazole or of its calcium salt. Despite the usefulness of 3-hydroxy-5-methylisoxazole and derivatives thereof, there is, therefore, a need to improve the residual effectiveness of these compounds.
Hitherto, it has been considered an advantage of 3-hydroxy-5-methylisoxazole and derivatives thereof that these compounds are readily decomposed in the soil, ultimately to carbon dioxide, thus leaving few residues and reducing take-up by the plants, which could lead to incorporation of the compounds in the food chain. Such incorporation is always thought to be best avoided even though these compounds are notably non-toxic to animals, including humans.
We have now, however, surprisingly found that the administration of an antimicrobial agent in association with 3-hydroxy-5-methylisoxazole or a salt thereof will inhibit decomposition of the 3-hydroxy-5-methylisoxazole and prolong its period of effectiveness, without ultimately preventing that decomposition, thus maintaining the known safety advantages of these compounds. Furthermore, we have found that the improvement in the residual activity in the soil is greater than could be predicted simply from the inhibition of decomposition of the compound.
We have also discovered that the hitherto unknown dihydrate of the calcium salt of 3-hydroxy-5-methylisoxazole has particular advantages over the 3-hydroxy-5-methylisoxazole itself and its known salts, as explained in detail hereafter.